The proton pump

At the start of a cycle, a T unit holds an ATP molecule. Then ADP and a Pi group migrate into the L site, and as it closes into T, the earlier T site opens into O and releases its ATP. The ADP and P, in the T site meanwhile condense into ATP, 

Flgt 8.20 The mechanism of action of H -ATPase, a molecular motor that transports protons across the mitochondrial membrane and catalyzes either the formation or hydrolysis of ATP. The yellow shapes represent the species ADP, ATP, and P,. 

Several key aspects of this mechanism have been confirmed experimentally. For example, the rotation of a y subunit has been portrayed directly by using single-molecule spectroscopy In the laboratory 12.6). 

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Feng Zhou, Andreas Windemuth, and Klaus Schulten. Molecular-dynamis study of the proton pump cycle of bacteriorhodopsin. Biochem., 32(9) 2291-2306, 1993. 

Moreover, receptors also control gastric acid release, although some marked species dependence is noticed (8). However, appHcation of agonists in this area does not seem to be probable the antagonists and the proton pump inhibitors serve quite weU. 

The discovery of the antiulcer activity of H2 antihistamine antagonists has revolutionized the treatment of that disease. A benzimidazole. Omeprazole (55), inhibits gastric secretion and subsequent ulcer formation by a quite different mechanism. Studies at the molecular level suggest that this compound inhibits K /H dependent ATPase and consequently shuts down the proton pumping action of this enzyme system. 

C1C-6 is a late endosomal chloride transporter. Its disruption in mice led to lysosomal storage disease. C1C-7 is expressed in late endosomes and lysosomes. It needs Ostml as (3-subunit [3]. The disruption of either C1C-7 or Ostml in mice and man leads to severe osteopetrosis, retinal degeneration, and a severe lysosomal storage disease. ClC-7/Ostml is highly expressed in osteoclasts. In these cells, it is inserted together with the proton pump into the specialized plasma membrane ( ruffled border ) that faces the reabsorption lacuna. Osteoclasts are still present in C1C-7 knockout... 

The proton pump is the gastric H,K-ATPase, which secretes hydronium ions, H30+, in exchange forK+ into the secretory canaliculus generating a pH of <1.0 in... 

The proton pump inhibitors are particularly important in the treatment of Helicobacter pylori in patients with active duodenal ulcers. Helicobacter pylori (H. pylori) has been implicated as a causative organism in a type of chronic gastritis and in a large number of cases of peptic and duodenal ulcers. 

The proton pump inhibitors suppress gastric acid secretion by blocking the final step in the production of gastric acid by the gastric mucosa... 

The proton pump inhibitors are used for treatment or symptomatic relief of various gastric disorders, including gastric and duodenal ulcers, GERD, or pathological hypersecretory conditions. Painful, persistent heartburn 2 or more days a week may indicate acid reflux disease which can erode the delicate lining of the esophagus,... 

The most common adverse reactions seen with the proton pump inhibitors include headache, diarrhea, and abdominal pain. Other less common adverse reactions include nausea, flatulence, constipation, and dry mouth. 

The proton pump inhibitors are contraindicated in patients who have hypersensitivity to any of the drags. Omeprazole (Pregnancy Category C) and lansoprazole, rabeprazole, and pantoprazole (Pregnancy Category B) are contraindicated during pregnancy and lactation. The proton pump inhibitors are used cautiously in older adults and in patients with hepatic impairment. 

PROTON PUMP INHIBITORS. The adverse reactions of the proton pump inhibitors are usually mild. The most common adverse reactions associated with file proton... 

Interaction of the food with the gastric mucosal layer is the normal trigger for gastric cells to release gastrin, which is then carried by the bloodstream to the parietal cells. Calcium ions and cyclic AMP act as intracellular messengers in the transfer of the signal from the receptors to the proton pumps of parietal cells where the acid is generated. 

Friedrich, T., Steinmuller, K., Weiss, H. (1995). The proton-pumping respiratory complex I of bacteria and mitochondria and its homologue in chloroplasts. (Review). FEBS Letters 367, 107-111. 

The Langmuir-Blodged (LB) technique allows one to form a monolayer at the water surface and to transfer it to the surface of supports. Formation of the BR monolayer at the air/water interface, however, is not a trivial task, for it exists in the form of membrane fragments. These fragments are rather hydrophilic and can easily penetrate the subphase volume. In order to decrease the solubility, the subphase usually contains a concentrated salt solution. The efficiency of the film deposition by this approach (Sukhorukov et al. 1992) was already shown. Nevertheless, it does not allow one to orient the membrane fragments. Because the hydrophilic properties of the membrane sides are practically the same, fragments are randomly oriented in opposite ways at the air/water interface. Such a film cannot be useful for this work, because the proton pumping in the transferred film will be automatically compensated i.e., the net proton flux from one side of the film to the other side is balanced by a statistically equal flux in the opposite direction. 

Horn J. The proton-pump inhibitors Similarities and differences. Clin Ther 2000 22 266-280. 

Other agents that appear to be safe for use in pregnancy include the proton pump inhibitors, sucralfate, and meto-clopromide (Table 44-5). The proton pump inhibitor with the largest body of human safety data during pregnancy is omeprazole.24... 

Belevich I, Verkhovsky MI, Wikstrom M (2006) Proton-coupled electron transfer drives the proton pump of cytochrome c oxidase. Nature 440 829-832. 

Hydrochloric acid (HCl), a strong acid that dissociates into an H+ and a CP ion, is produced by the parietal cells. These ions are actively transported into the lumen of the stomach by the proton pump. Functions of HCl include ... 

The answer is d. (Hardman, pp 907-909J Omeprazole inhibits H+,K+,ATPase, which effectively stops the proton pump and thus prevents the formation of gastric acid. It is the most effective agent in severe cases of ulceration and esophageal reflux. 

The answer is d. (Hardman 7 pp 907—909J The main action of omeprazole is the inhibition of secretion of gastric acid Because it is a specific inhibitor of the proton pump (H+,K+,ATPase), other actions are secondary to the marked decline of acid secretion. As a result of the reduction of gastric acidity, there is increased secretion of gastrin leading to hyper-gastrinemia. 

Acid reflux and heartburn are conditions that affect many of us from time to time. Exhibit 1.4 describes the proton pump inhibitor, Nexium, and its predecessor, Prilosec, and how they work as antiulcerants. 

Figure 9.9 A diagrammatic representation of the mechanism of the proton pump that transfers protons across the inner mitochondrial membrane. The process can be divided into three parts ...

Omeprazole (p. 167) can cause maximal inhibition of HCl secretion. Given orally in gastric juice-resistant capsules, it reaches parietal cells via the blood. In the acidic milieu of the mucosa, an active metabolite is formed and binds covalently to the ATP-driven proton pump (H+/K+ ATPase) that transports H+ in exchange for IC into the gastric juice. Lansoprazole and pantoprazole produce analogous effects. The proton pump inhibitors are first-line drugs for the treatment of gastroesophageal reflux disease. 

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